The OLIG1 gene encodes the oligodendrocyte lineage transcription factor 1, a basic helix-loop-helix transcription factor (bHLH). OLIG1 is expressed in oligodendrocyte precursors and mature oligodendrocytes (Lu, Yuk et al. 2000; Zhou, Wang et al. 2000; Balasubramaniyan, Timmer et al. 2004; Othman, Frim et al. 2011). These bHLH transcription factors are important in cortical brain development. Some research indicates that OLIG1 may also be expressed in oligodendroglial or other brain tumors (Brena, Morrison et al. 2007; Wu, Richard et al. 2012), and thus an OLIG1-based Mini-Promoter could be used to identify and treat such cells (Hoang-Xuan, Aguirre-Cruz et al. 2002). Furthermore, disorders such as multiple sclerosis wherein there are defects in myelination of neuronal cells, may require the functioning of OLIG1-expressing cells in order to remyelinate axons, implicating the use of an OLIG1 Mini-Promoter in therapeutic contexts (Burton 2005; Goris, Yeo et al. 2006; Arnett, Fancy et al. 2004; Maire, Wegener et al. 2010; Liu, Jiang et al. 2011; Whitman, Blanc et al. 2012). Other evidence implicates OLIG1-dysfunction in neurodevelopmental disorders, such as Down syndrome (Chakrabarti, Best et al. 2010).
There is a need for a characterized human OLIG1 promoter for gene expression, for instance in human gene therapy applications. It is particularly useful to identify small promoter elements that are sufficient to drive expression in regions of the brain, for instance in oligodendrocytes. Such small promoter elements, or “mini-promoters” are particularly useful in certain applications, for instance their compact size make “mini-promoters” more amenable to insertion into space-limited viral vectors used in gene therapy applications.
OLIG1 promoter elements are described in the art, including the promoter known as Ple151 (Portales-Casamar, Swanson et al. 2010). Other OLIG1-based promoters include transcriptional studies of the murine homolog (Olig1) that showed a 289 bp fragment from the promoter region could drive the expression of a reporter gene (Gong, Lin et al. 2008). In addition, a previous study also investigated conserved and non-conserved functional elements in the murine homologs of OLIG1 and OLIG2 and identified a class of conserved enhancer elements located upstream of OLIG2 (Friedli, Barde et al. 2011).